Cervical cancer is the third most common cancer among women worldwide with 400,000 newly diagnosed cases every year. Cervical cancer is the most common cancer of women in most developing countries, where it accounts for as many as one in four female cancers. It occurs much less frequently in developed countries. In the US, there are about 15,000 new diagnosed cases each year and about 1/3 of these women die of the malignant form of the disease. This incidence in women in the US varies among ethnic groups; it is twice as prevalent in black women than in white women. Cervical HPV infection is extremely common in sexually active young women. Peak prevalence is seen between 15 to 25 years of age and varies from 25 to 40%.
Information on HPV prevalence worldwide is inconsistent since there is no standardized method of detection. There is virtually no data on HPV prevalence in developing countries. Many people infected with HPV may not develop symptoms for several months or have access to health care facilities. An estimated 60% of HPV prevalence depends largely on the accuracy of the detection methods.
¤ Most cancers occur in the transformation zone of the cervix, where the columnar cells of the endocervix form a junction with the stratified squamous epithelium of the exocervix. About 85% of cervical cancers are squamous cell cancers. Most other cases are adenocarcinomas.
¤ Lesions that are destined to become maliganant squamous cell carcinomas usually undergo a series of dysplastic changes over a time span of many years. The severity of the dysplasia is rated by the degree to which the squamous epithelium is replaced by basaloid cells, where the most severe dysplasia has the entire thickness displaced. Most dysplasias do not progress and resolve spontaneously.
¤ A world-wide study of almost 1,000 cervical cancers indicated that more than 90% contain HPV DNA. Although more than 20 types were found in the tumors, four types (HPV-16, HPV-18, HPV-31, and HPV-45) accounted four about 80% of the HPV-positive cancers.
¤ HPV-16 appears to be the most common type of HPV found in cervical cancers. HPV-18 is the predominant type in adenocarcinomas, and HPV-16 is the most common type in squamous cell cancers.
¤ In mildly dysplasic lesions, each of the ORFs appears to be expressed, mainly in the upper layers of the epithelium, but in high grade dysplasias, a more restricted number of ORFs are expressed, primarily E6 and E7, and their expression is found primarily in the basal, proliferating layer of the epithelium.
Although infection with HPV is raises the risk of developing cervical cancer and may be necessary for the development of cervical cancer, it is clearly not sufficient. Other factors must collaborate to cause oncogenesis. Some changes can be virus specific: e.g. viral integration into the host genome leading to decreased expression of some viral genes; increased expression of E6 and E7; and selective growth advantage. Other alterations include genetic alterations of cellular genes. Tumors typically have several cellular alterations that lead to loss or gain of function of some genes involved in growth and cell-cycle regulation. There are also environmental risk factors, such as smoking or immunosuppression, which contribute to the development of cervical cancer.